Studies Shed More Light on Acute Hepatitis C among HIV Positive Men in the U.S. and Europe

By Liz Highleyman

Since around 2000, clinicians have been reporting outbreaks of apparently sexually transmitted acute hepatitis C virus (HCV) infection among mostly HIV positive men in cities in the U.K. and continental Europe. More recently, such cases have also been described in Australia and the U.S., and one group has found that HCV infection in people who already have HIV may lead to unusually rapid liver disease progression.

While most of these acute hepatitis C cases have been identified in HIV positive men who have sex with men (MSM), some experts have suggested that because people with HIV on antiretroviral therapy receive regular liver function monitoring, it is possible to catch liver enzyme elevations that signal HCV infection in its early stages. By contrast, HIV negative people are seldom screened for HCV (unless they have a traditional risk factor such as injection drug use), and therefore asymptomatic acute HCV infection may go unnoticed and untreated.

At the recent 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD) in Washington, DC, 2 research teams provided further information on HCV coinfection in HIV positive and HIV negative MSM.

U.S.

In the first study, Lynn Taylor from Brown University in Providence, RI, and colleagues screened "at-risk" patients at an HIV clinic for acute HCV coinfection. At-risk attendees were defined as men who did not already have chronic hepatitis C and who reported sexual and/or drug-related risk behaviors within the prior 6 months.

Participants were prospectively enrolled in a 9-month study of a screening strategy to identify acute HCV infection using routine blood tests. Every 3 months, ALT was measured and patients completed a risk survey. Those who experienced a rise in ALT received HCV RNA testing (cut-off < 650 IU/mL).

Measurable HCV RNA in the absence of HCV antibodies may indicate acute hepatitis C, during the "window period" before the body has produced enough antibodies to register on the test. Alternatively, HIV positive people with severe immune suppression may not be able to mount a significant antibody response.

Out of 194 HCV antibody negative clinic attendees initially screened over 28 weeks of recruitment, 58 were enrolled in the study. Almost all (97%) were men, the mean age was 42 years, 74% were white, 5% were black, and 14% were Hispanic; nearly three-quarters had attended college.

Results

In the prior 3 months, 56% of men reported unprotected insertive anal intercourse and 52% reported receptive anal intercourse.

13% said they engaged in unprotected fisting.

11% said they saw blood on their or their partner's genitals or anus during sex.

77% had a history of sexually transmitted infections (STIs).

23% reported having sex with 4-10 persons and 14% had more than 10 sex partners in the past 3 months.

28% said they had participated in group sex.

24% had met a sex partner via the Internet.

In the prior 3 months 42% had used poppers, 27% used cocaine, 22% took erectile dysfunction drugs, 12% used amphetamines, 7% used ecstasy, and 7% used heroin.

33% reported snorting or inhaling drugs (20% said they shared straws) and 4% reported injection drug use.

30% reported having unprotected sex under influence of drugs or alcohol.

Despite these risk factors, just over half (51%) rated their risk of HCV infection as low.

1 case of acute hepatitis C was identified, in a 56-year-old MSM injection drug user; the man declined anti-HCV treatment and went on to develop chronic hepatitis C.

Assuming they would have identified anyone who contracted HCV within the 3 months prior to testing, the incidence was 1 case per 14.8 person-years, for an annual incidence rate of 6.8% (since HCV seroconversion was tracked over 3 months, the annual incidence rate estimate was the 3-month figure times 4).

Based on these findings, the investigators concluded, "Traumatic sexual and drug practices that may transmit HCV are prevalent and not appreciated in a well-educated cohort in HIV care."

Amsterdam

In the second study, Anouk Urbanus and colleagues analyzed the prevalence of HCV and determinants of infection among MSM visiting a large STI clinic in Amsterdam.

In May and November 2007 and again in April 2008, 3125 clinic attendees completed an anonymous biannual survey; 689 of them (22%) were MSM. In addition, they were interviewed about risk factors for blood-borne and sexually transmitted infections and screened for HIV and HCV antibodies. HIV positive men also received HCV RNA tests, regardless of HCV antibody status.

Results

2 out of 532 HIV negative MSM (0.4%) were found to be infected with HCV, compared with 28 out of 157 HIV positive MSM (17.8%).

9 of the 28 HIV-HCV coinfected MSM (32.1%) tested HCV antibody negative but HCV RNA positive, indicating possible acute HCV infection.

Over time, the HCV prevalence among HIV positive MSM increased:

May 2007: 7 out of 48 tested (14.6%);
November 2007: 7 out of 42 (16.7%);
April 2008: 14 out of 67 (20.9%).

31.8% of the HCV positive MSM were previously unaware of their HCV status.

Half of the HIV negative MSM and 17.9% of the HIV positive MSM reported ever injecting drugs.

In multivariate analysis, HIV infection (odd ratio [OR] 38.4), fisting (OR

15.0) and injection drug use (OR 15.5) were significantly associated with HCV infection.

Fisting itself was strongly correlated with the use of sex toys, group sex, bleeding during sex, and use of the club drug GHB.

Among the 22 out of 28 (78.6%) HIV-HCV coinfected MSM with detectable HCV RNA, phylogenetic analysis showed a high degree of clustering.

20 of these 22 (90.9%) carried HCV genotype 1a (17 cases) and 4d (3 cases) strains that have previously been associated with acute hepatitis C outbreaks among MSM.

"We found a high and increasing HCV prevalence in HIV-infected MSM attending the STI clinic," the investigators concluded. "HCV prevalence in HIV-infected MSM was very low (1-4%) before 2000, this trend and the large proportion of acute infections suggest a rapid spread of HCV."

Independent of injection drug use, they continued, "rough sexual techniques were associated with HCV and phylogenetic analysis reveals the presence of MSM-specific HCV strains, supporting sexual transmission."

"Targeted preventions like raising awareness and routine testing are needed to stop the further spread among HIV-infected MSM, and a possible spill over to HIV negative MSM," they recommended.

4/7/09

References

LE Taylor, AK DeLong, PM Gholam, and others. Screening for Acute Hepatitis C Virus Infection (AHCV) among At-Risk Patients in an HIV Clinic. 13th International Symposium on Viral Hepatitis and Liver Disease (13th ISVHLD). Washington, DC. March 20-24, 2009. Abstract OP-173.

AT Urbanus, TJ W van de Laar, J Schinkel, and others. Rising HCV Prevalence among HIV-infected Men Who Have Sex with Men (MSM) in Amsterdam: An Expanding Epidemic. 13th ISVHLD. Abstract OP-170.